{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T16:00:52Z","timestamp":1785427252690,"version":"3.56.0"},"reference-count":88,"publisher":"MDPI AG","issue":"13","license":[{"start":{"date-parts":[[2026,6,24]],"date-time":"2026-06-24T00:00:00Z","timestamp":1782259200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Ministry of Science, Technological Development and Innovation of the Republic of Serbia","award":["451-03-33\/2026-03\/200019"],"award-info":[{"award-number":["451-03-33\/2026-03\/200019"]}]},{"name":"Ministry of Science, Technological Development and Innovation of the Republic of Serbia","award":["451-03-33\/2026-03\/200161"],"award-info":[{"award-number":["451-03-33\/2026-03\/200161"]}]},{"award":["451-03-33\/2026-03\/200019"],"award-info":[{"award-number":["451-03-33\/2026-03\/200019"]}],"id":[{"id":"https:\/\/ror.org\/01znas443","id-type":"ROR","asserted-by":"publisher"}]},{"award":["451-03-33\/2026-03\/200161"],"award-info":[{"award-number":["451-03-33\/2026-03\/200161"]}],"id":[{"id":"https:\/\/ror.org\/01znas443","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Adequate placental development and function, prerequisites for the development of a healthy fetus, rely on controlled trophoblast invasion into the decidua and remodeling of the spiral arteries. These tightly regulated processes involve epithelial\u2013mesenchymal transition (EMT) and endovascular differentiation of trophoblast cells. Taxifolin (dihydroquercetin), a natural flavonoid with various pharmacological effects, previously showed cytoprotective, antioxidant, and anti-inflammatory activity on trophoblast cells. Given that the literature indicates that this flavonoid suppresses EMT and can affect angiogenesis across different cell types, we investigated the potential of taxifolin (10 and 100 \u00b5M) to modulate invasion and endothelial-like differentiation in human extravillous trophoblast HTR-8\/SVneo cells by functional tests. Expression of different molecular markers relevant to these processes was evaluated at the mRNA and protein levels. Our results showed that taxifolin inhibited invasion of HTR-8\/SVneo cells, involving downregulation of integrin \u03b15 subunit and modulation of MMP-2 and MMP-9 mRNA expression and secretion. No changes in the concentrations of secreted TIMP-1 and TIMP-2 were observed following taxifolin treatment. Furthermore, downregulation of N-cadherin and vimentin in treated trophoblast cells indicated suppression of EMT. Taxifolin inhibited endothelial-like differentiation of HTR-8\/SVneo cells, as evidenced by reduced tube formation and downregulation of VE-cadherin in treated cells. Moreover, expression of TGFB1 was upregulated in treated cells, as were levels of phosphorylated SMAD2\/3, indicating involvement of TGF-\u03b2 signaling in TF-induced effects on trophoblast cells. The in vitro effects of taxifolin on suppression of trophoblast invasion, EMT, and endothelial-like differentiation highlight its potential impact on placental development processes.<\/jats:p>","DOI":"10.3390\/cells15131152","type":"journal-article","created":{"date-parts":[[2026,6,25]],"date-time":"2026-06-25T01:03:56Z","timestamp":1782349436000},"page":"1152","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Taxifolin Inhibits Invasion and Endovascular Differentiation of Extravillous Trophoblast HTR-8\/SVneo Cells"],"prefix":"10.3390","volume":"15","author":[{"given":"Aleksandra","family":"Viloti\u0107","sequence":"first","affiliation":[{"name":"Department for Biology of Reproduction, Institute for the Application of Nuclear Energy (INEP), University of Belgrade, 11080 Belgrade, Serbia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Janko","family":"Legner","sequence":"additional","affiliation":[{"name":"Department for Biology of Reproduction, Institute for the Application of Nuclear Energy (INEP), University of Belgrade, 11080 Belgrade, Serbia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"\u017danka","family":"Boji\u0107-Trbojevi\u0107","sequence":"additional","affiliation":[{"name":"Department for Biology of Reproduction, Institute for the Application of Nuclear Energy (INEP), University of Belgrade, 11080 Belgrade, Serbia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marija","family":"Brui\u0107","sequence":"additional","affiliation":[{"name":"Department of Pathobiology, Faculty of Pharmacy, University of Belgrade, 11221 Belgrade, Serbia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5570-883X","authenticated-orcid":false,"given":"Biljana","family":"Spremo-Potparevi\u0107","sequence":"additional","affiliation":[{"name":"Department of Pathobiology, Faculty of Pharmacy, University of Belgrade, 11221 Belgrade, Serbia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8292-4853","authenticated-orcid":false,"given":"Milica","family":"Jovanovi\u0107 Krivoku\u0107a","sequence":"additional","affiliation":[{"name":"Department for Biology of Reproduction, Institute for the Application of Nuclear Energy (INEP), University of Belgrade, 11080 Belgrade, Serbia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1182-4895","authenticated-orcid":false,"given":"Andrea","family":"Pirkovi\u0107","sequence":"additional","affiliation":[{"name":"Department for Biology of Reproduction, Institute for the Application of Nuclear Energy (INEP), University of Belgrade, 11080 Belgrade, Serbia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,6,24]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"345","DOI":"10.1007\/s00018-022-04377-0","article-title":"Early Human Trophoblast Development: From Morphology to Function","volume":"79","author":"Gauster","year":"2022","journal-title":"Cell. 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